Methods of making cocrystals

Abstract

Disclosed are processes for preparing cocrystals, including processes for scaling up of cocrystal formation, as well as scalable processes for preparing cocrystals. Also disclosed are processes for scaled-op preparation of pterostilbene, progesterone, p-coumaric, and minoxidil cocrystals. Minoxidil cocrystals, such as minoxidil:benzoic acid 1:1 monohydrate cocrystals are also disclosed herein.

1 .- 79 . (canceled) 
     
     
         80 . A process for making a cocrystal of a compound and a coformer comprising combining the compound dissolved in a solvent solution with the coformer dissolved in the solvent solution wherein the solubilities of the compound and the coformer in the solvent solution are each of a value sufficiently similar to form a cocrystal of the compound and the coformer as a single crystal phase, and precipitating a cocrystal of the compound and the coformer from the solvent solution. 
     
     
         81 . The process of  claim 80  wherein the solubilities of the compound and the coformer in the solvent solution are within a factor of ten. 
     
     
         82 . The process of  claim 80 , wherein the compound is a salt. 
     
     
         83 . The process of  claim 81 , wherein the compound is a salt. 
     
     
         84 . The process of  claim 80 , wherein the solvent solution comprises two or more solvents. 
     
     
         85 . The process of  claim 81 , wherein the solvent solution comprises two or more solvents. 
     
     
         86 . The process of  claim 80 , wherein the compound is a pharmaceutical compound. 
     
     
         87 . The process of  claim 81 , wherein the compound is a pharmaceutical compound. 
     
     
         88 . The process of  claim 80 , wherein the coformer is a pharmaceutical compound. 
     
     
         89 . The process of  claim 81 , wherein the coformer is a pharmaceutical compound. 
     
     
         90 . The process of  claim 80 , wherein the coformer is a carboxylic acid, an amino acid, a sugar, a flavoring agent, or a nutraceutical. 
     
     
         91 . The process of  claim 81 , wherein the coformer is a carboxylic acid, an amino acid, a sugar, a flavoring agent, or a nutraceutical. 
     
     
         92 . The process of  claim 80 , wherein the solubility of the compound in the solvent solution is equal to the solubility of the coformer in the solvent solution. 
     
     
         93 . The process of  claim 80 , wherein the solubility of the compound in the solvent solution is within a factor of 2 of the solubility of the coformer in the solvent solution. 
     
     
         94 . The process of  claim 80 , wherein the cocrystal yield is greater than 70%. 
     
     
         95 . The process of  claim 81 , wherein the cocrystal yield is greater than 70%. 
     
     
         96 . The process of  claim 80 , further comprising the step of seeding the solvent solution. 
     
     
         97 . The process of  claim 81 , further comprising the step of seeding the solvent solution. 
     
     
         98 . The process of  claim 97  wherein the seeding comprises adding one or more seed crystals of the cocrystal to the solvent solution. 
     
     
         99 . The process of  claim 80  wherein the cocrystal of the compound and the coformer from the solvent solution are in the single crystal phase.